A tactical missile defense unit, commonly abbreviated TMD, is a unit that is capable of stopping an incoming tactical missile. Each faction has a structure that provides this defense and some units, such as Cruisers and Battleships, feature on-board tactical missile defense systems. The shipboard systems have a range of 50, while the land based structures' ranges are 30. The CybranLoyalist actually deflects missiles back at the launcher, and is the only mobile land-based TMD platform.

Cybran, UEF and Seraphim TMD all use direct fire in shooting down tactical missiles. Aeon TMD differs from the other factions in that it doesn't actually target missiles, instead a bubble will launch out of the TMD and attract multiple missiles, though has a slow rate of fire. The direct fire the other factions use as a defense is much more effective when multiple tmd's are built. Cybran have the most efficient TMD of the direct fire TMD due to the instant hit nature of the laser, unlike the Seraphim and UEF TMD, which often launches multiple projectiles at the same tactical missile.

The Seraphim TMD naturally turn 50% faster than its UEF counterpart, but it also fires half as fast.